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Y. Yafai, M. Niemeyer, T. Yasukawa, A. Nishiwaki, P. Wiedemann, A. G. King, W. Eichler; Inhibition of Experimental Choroidal Neovascularization by the VEGF Receptor Inhibitor Pazopanib (GW786034B). Invest. Ophthalmol. Vis. Sci. 2008;49(13):534.
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Inhibition of vascular endothelial growth factor (VEGF) signaling has shown great promise for the treatment of ocular neovascular disease. Current anti-VEGF therapies, while efficacious, require dosing by frequent intravitreal injections that are inconvenient for patients. However, VEGF signaling inhibitors demonstrating more convenient dosing regimens could lead to increased treatment options for neovascular ocular diseases, such as wet form of age-related macular degeneration and diabetic macular edema. Pazopanib (GW786034B) is a potent multi-targeted tyrosine kinase inhibitor that antagonizes receptors for VEGF, PDGF, and stem cell growth factor. Here we describe the assessment of this drug in a well-established model of ocular neovascularization following topical administration via eye drops.
Pazopanib (GW786034B), was dosed daily at 5 mg/ml for one week by topical administration in a rat model of laser induced choroidal neovascularization (CNV). Before and after the treatment period areas of CNV lesions were quantitated using fluorescence angiography, and the thickness of CNV complexes was determined histologically.
The intensity of fluorescein leakage from the photocoagulated lesions decreased significantly after pazopanib (GW786034B) treatment. Moreover, the thickness of the lesions was significantly reduced in eyes which received pazopanib (GW786034B) topically.
Topical dosing of pazopanib (GW786034B) effectively inhibits CNV in a rat model of CNV. These data suggest that pazopanib (GW786034B) and/ or compounds of this class may prove useful for the treatment of a variety of ocular neovascular diseases using a convenient topical dosing regimen.
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